MicroRNA-26b inhibits metastasis of osteosarcoma via targeting CTGF and Smad1

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• 作者：Guoqing Duan ; Chunfeng Ren ; Yuanmin Zhang ; Shiqing Feng
• 关键词：Osteosarcoma ; MicroRNA ; CTGF ; Smad1 ; MMP2 ; Metastasis
• 刊名：Tumor Biology
• 出版年：2015
• 出版时间：August 2015
• 年：2015
• 卷：36
• 期：8
• 页码：6201-6209
• 全文大小：4,094 KB
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• 作者单位：Guoqing Duan (1) (2)
  Chunfeng Ren (3)
  Yuanmin Zhang (2)
  Shiqing Feng (1)
  
  1. Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, 300052, People’s Republic of China
  2. Department of Joint and Sports Medicine, Affiliated Hospital of Jining Medical College, Jining, 272029, People’s Republic of China
  3. Department of Rheumatology, Jining First People’s Hospital, Jining, Shandong, 272111, People’s Republic of China
  
• 刊物主题：Cancer Research;
• 出版者：Springer Netherlands
• ISSN：1423-0380

文摘

Downregulation of miR-26b has been found in various cancers, but it has never been investigated in osteosarcoma. In this study, we demonstrated downregulation of miR-26b in osteosarcoma tissues, negatively correlated with the expression of connective tissue growth factor (CTGF) and Smad1. Luciferase reporter assay confirmed the interaction of miR-26b with the 3-untranslated regions (UTRs) of CTGF and Smad1. Transfection of miR-26b in osteosarcoma cells suppressed the expression of CTGF and Smad1, suggesting CTGF and Smad1 as direct targets of miR-26b. Overexpression of miR-26b inhibited the migration of osteosarcoma cells, which was reversed by overexpression of CTGF or Smad1. Knockdown of CTGF by small interfering RNA (siRNA) interference blocked the activation of Smad1, ERK1/2, and MMP2, which was opposite to the overexpression of CTGF. Differently, Smad1 did not significantly affect CTGF level, but mediated ERK1/2 phosphorylation and MMP2 activation. Furthermore, miR-26b inhibited lung metastasis of osteosarcoma in vivo. Our data indicated that downregulation of miR-26b in osteosarcoma elevated the levels of CTGF and Smad1, facilitating osteosarcoma metastasis. Keywords Osteosarcoma MicroRNA CTGF Smad1 MMP2 Metastasis